Background/Disease Information: Francisella tularensis is a small, gram-negative bacteria that causes tularemia, also known as rabbit or deerfly fever. Because it has a very low infectious does, is highly virulent, and can easily be spread aerosol, it US government classifies it as a category A pathogen and a potential agent of bioterrorism. Tularemia usually is not transmitted from human to human, but rather contracted via contact with infected animals (birds, reptiles, fish, invertebrates, or mammals) or hosts like ticks or mosquitoes. Aerosols containing the bacteria are often created when brushcutting or lawnmowing disturbs carcasses or when hunters are skinning animals, and the disease can be contacted via inhalation of the bacteria. Tularemia is also often contracted via ingestion of contaminated water, soil, or food. Symptoms of tularemia in humans include high fever, lethargy, skin lesions. It is often fatal. Currently, tularemia is treated only with antibiotics like streptomycin. A live vaccine is available, but it is only used in extremely high risk groups.
Essentiality of this protein:Francisella tularensis cannot survive in a macrophage without IglC. Mutant strains of Francisella tularensis without the IglC gene cannot survive or reproduce [1].
Complex of proteins: IglC is part of an island complex of proteins including IglA and IglB. IglA and IglB form an outer tube structure that surrounds an inner tube of IglC subunits [2].
Druggable Target (list number or cite evidence from a paper/database showing druggable in another organism): Qingmei, J.; Lee, B.; Clemens, D. L.; Bowen, R. A.; Horwitz, M. A. Recombinant attenuated Listeria monocytogenes vaccine expressing Francisella tularensis IglC induces protection in mice against aerosolized Type A F. tularensis. Elsevier 2009, 27(8) 1216-1229.
EC#: There is no EC number for this protein yet.
Assay Information: Ascorbic acid (shown below) found to be an inhibitor Citation for the article containing the assay information: McRae, S; Pagliai, FA; Mohapatra, NP; Gener, A; Mahmou, AS; Gunn, JS; Lorca, GL; Gonzalez, CF Inhibition of AcpA phosphatase activity with ascorbate attenuates Francisella tularensis intramacrophage survival. J Biol Chem 285:5171-7 (2010)
Structure Available: Yes, island protein C in Francisella tularensis is available in the PDB (ID: 2QWU)
Expression Information (has it been expressed in bacterial cells): Yes, it’s been expressed in BL21 cells.
Molar Extinction coefficient of protein at 280 nm wavelength: 0.522 assuming that all pairs of Cys residues form cystines, or 0.511 assuming that all Cys residues are reduced.
1. Lauiano, C. M.; Barker, J. R.; Yoon, S.; Nano, F. E.; Arulanandam, B. P.; Hassett, D. J.; Klose, K. E. MglA regulates transcription of virulence factors necessary for Francisella tularensis intraamoebae and intramacrophage survival. Proceedings of the National Academy of Sciences of the United States of America 2004, 101(12), 4246-4249.
2. de Bruin, O. M.; Duplantics, B. N.; Ludu, J. S.; Hare, R. F.; Nix, E. B.; Schmerk, C. L.; Robb, C. S.; Boraston, A. B.; Heuffer, K.; Nano, F. E. The biochemical properties of the Francisella pathogenicity island (FPI)-encoded proteins IglA, IglB, IglC, PdpB and DotU suggest roles in type VI secretion. Microbiology 2011, 157, 3483-3491.
NCBI Gene #: 3191591
Organism: Francisella tularensis SchuS4
Etiologic Risk Group: NIAID Category A Pathogen
Background/Disease Information:
Francisella tularensis is a small, gram-negative bacteria that causes tularemia, also known as rabbit or deerfly fever. Because it has a very low infectious does, is highly virulent, and can easily be spread aerosol, it US government classifies it as a category A pathogen and a potential agent of bioterrorism. Tularemia usually is not transmitted from human to human, but rather contracted via contact with infected animals (birds, reptiles, fish, invertebrates, or mammals) or hosts like ticks or mosquitoes. Aerosols containing the bacteria are often created when brushcutting or lawnmowing disturbs carcasses or when hunters are skinning animals, and the disease can be contacted via inhalation of the bacteria. Tularemia is also often contracted via ingestion of contaminated water, soil, or food. Symptoms of tularemia in humans include high fever, lethargy, skin lesions. It is often fatal. Currently, tularemia is treated only with antibiotics like streptomycin. A live vaccine is available, but it is only used in extremely high risk groups.
Link to TDR Targets page: None
Link to Gene Database page: http://www.ncbi.nlm.nih.gov/nucleotide/109703076?report=genbank&log$=nucltop&blast_rank=6&RID=PA2ZP2GP015
Essentiality of this protein: Francisella tularensis cannot survive in a macrophage without IglC. Mutant strains of Francisella tularensis without the IglC gene cannot survive or reproduce [1].
Complex of proteins: IglC is part of an island complex of proteins including IglA and IglB. IglA and IglB form an outer tube structure that surrounds an inner tube of IglC subunits [2].
Druggable Target (list number or cite evidence from a paper/database showing druggable in another organism):
Qingmei, J.; Lee, B.; Clemens, D. L.; Bowen, R. A.; Horwitz, M. A. Recombinant attenuated Listeria monocytogenes vaccine expressing Francisella tularensis IglC induces protection in mice against aerosolized Type A F. tularensis. Elsevier 2009, 27(8) 1216-1229.
EC#: There is no EC number for this protein yet.
Assay Information: Ascorbic acid (shown below) found to be an inhibitor
Citation for the article containing the assay information:
McRae, S; Pagliai, FA; Mohapatra, NP; Gener, A; Mahmou, AS; Gunn, JS; Lorca, GL; Gonzalez, CF Inhibition of AcpA phosphatase activity with ascorbate attenuates Francisella tularensis intramacrophage survival. J Biol Chem 285:5171-7 (2010)
Structure Available: Yes, island protein C in Francisella tularensis is available in the PDB (ID: 2QWU)
Expression Information (has it been expressed in bacterial cells): Yes, it’s been expressed in BL21 cells.
Image of protein: From the PDB, ID: 2QWU
Amino Acid Sequence:
MIMSEMITRQQVTSGETIHVRTDPTACIGSHPNCRLFIDSLTIAGEKLDKNIVAIDGGED
VTKADSATAAASVIRLSITPGSINPTISITLGVLIKSNVRTKIEEKVSSILQASATDMKI
KLGNSNKKQEYKTDEAWGIMIDLSNLELYPISAKAFSISIEPTELMGVSKDGMRYHIISI
DGLTTSQGSLPVCCAASTDKGVAKIGYIAAA
Length of protein in Amino Acids: 211
Molecular Weight of your in kiloDaltons:22432.8
Molar Extinction coefficient of protein at 280 nm wavelength: 0.522 assuming that all pairs of Cys residues form cystines, or 0.511 assuming that all Cys residues are reduced.
TMpred graph Image:
CDS Gene Sequence:
ATGATTATGAGTGAGATGATAACAAGACAACAGGTAACAAGTGGCGAGACCATTCATGTG
AGAACTGATCCTACTGCATGTATAGGATCTCATCCTAATTGTAGATTATTTATTGATTCT
TTAACTATAGCTGGGGAGAAACTTGATAAAAATATCGTTGCTATAGATGGTGGAGAGGAT
GTCACGAAAGCTGATTCGGCTACAGCTGCTGCTAGTGTAATACGTTTATCTATAACGCCA
GGCTCTATAAATCCAACAATAAGTATTACTCTTGGTGTTCTAATTAAATCAAATGTTAGA
ACTAAAATTGAAGAGAAAGTTTCGAGTATATTACAAGCAAGTGCTACAGATATGAAAATT
AAGTTAGGTAATTCTAATAAAAAACAAGAGTATAAAACTGATGAAGCATGGGGTATTATG
ATAGATCTATCTAATTTAGAGTTATATCCAATAAGTGCTAAGGCTTTTAGTATTAGTATA
GAGCCAACAGAACTTATGGGTGTTTCAAAAGATGGAATGAGATATCATATTATATCTATA
GATGGTCTTACAACATCTCAAGGAAGTTTGCCAGTATGTTGCGCAGCTAGCACAGATAAA
GGAGTTGCTAAAATAGGATATATTGCAGCTGCATAG
GC% Content for gene: 34.12%
References:
1. Lauiano, C. M.; Barker, J. R.; Yoon, S.; Nano, F. E.; Arulanandam, B. P.; Hassett, D. J.; Klose, K. E. MglA regulates transcription of virulence factors necessary for Francisella tularensis intraamoebae and intramacrophage survival. Proceedings of the National Academy of Sciences of the United States of America 2004, 101(12), 4246-4249.
2. de Bruin, O. M.; Duplantics, B. N.; Ludu, J. S.; Hare, R. F.; Nix, E. B.; Schmerk, C. L.; Robb, C. S.; Boraston, A. B.; Heuffer, K.; Nano, F. E. The biochemical properties of the Francisella pathogenicity island (FPI)-encoded proteins IglA, IglB, IglC, PdpB and DotU suggest roles in type VI secretion. Microbiology 2011, 157, 3483-3491.